In recent clinical trials, researchers found that compounds that block the type1 cannabinoid (CB1) receptor were effective not only in reducing the weight of obese individuals, but also in reversing their associated insulin resistance, abnormal blood lipid profile and accumulation of fat in the liver. Unfortunately, these compounds also elicited depression and anxiety, making them unsuitable for therapeutic use. Studies in animal models of obesity have indicated that the beneficial metabolic effects of CB1 receptor blocking drugs is mediated, at least in part, by blockade of CB1 receptors in peripheral tissues, including the liver, fat and skeletal muscle cells, whereas their neuropsychiatric side effects are due to blockage of CB1 receptors in the brain. The investigators modified the chemical structure of currently available CB1-blocking drugs in a way that reduced their ability to penetrate the blood-brain barrier, but that did not affect their oral bioavailability, selectivity and high affinity for the CB1 receptor. The lab has made progress towards the completion of the following studies on JD3057: - Formulation development - Manufacture of drug product to support Phase 1 studies - Pharmacokinetic/absorption, distribution, metabolism, and excretion (PK/ADME) studies - Investigational New Drug (IND)-directed toxicology As a result of BrIDGs support, the collaborators were able to file an IND application, which was cleared by the Food and Drug Administration (FDA). The team is continuing to evaluate a high-dose formulation of JD3057.